Variant chr1-23310602-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PS1_ModeratePM2PP2PP5BP4

The ENST00000302271.11(HNRNPR):c.1754G>A(p.Arg585His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.

Frequency

Genomes: not found (cov: 32)

Consequence

HNRNPR
ENST00000302271.11 missense

Scores

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.86

Variant links:

Genes affected

HNRNPR (HGNC:5047): (heterogeneous nuclear ribonucleoprotein R) This gene encodes an RNA-binding protein that is a member of the spliceosome C complex, which functions in pre-mRNA processing and transport. The encoded protein also promotes transcription at the c-fos gene. Alternative splicing results in multiple transcript variants. There are pseudogenes for this gene on chromosomes 4, 11, and 10. [provided by RefSeq, Jul 2014]

HNRNPR links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PS1

Transcript ENST00000302271.11 (HNRNPR) is affected with MISSENSE_VARIANT having same AA change as one Pathogenic present in UniProt

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), HNRNPR. . Gene score misZ 3.5388 (greater than the threshold 3.09). Trascript score misZ 4.0437 (greater than threshold 3.09). GenCC has associacion of gene with intellectual disability, autosomal dominant 40, syndromic intellectual disability, neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities.

PP5

Variant 1-23310602-C-T is Pathogenic according to our data. Variant chr1-23310602-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 1710309.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-23310602-C-T is described in Lovd as [Pathogenic].

BP4

Computational evidence support a benign effect (MetaRNN=0.3281278). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HNRNPR	NM_005826.5 linkuse as main transcript	c.1754G>A	p.Arg585His	missense_variant	11/11	ENST00000302271.11	NP_005817.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HNRNPR	ENST00000302271.11 linkuse as main transcript	c.1754G>A	p.Arg585His	missense_variant	11/11	1	NM_005826.5	ENSP00000304405	P3	O43390-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Neurodevelopmental disorder with dysmorphic facies and skeletal and brain abnormalities

Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 13, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

0.0043

BayesDel_noAF

Benign

-0.23

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.56

.;.;D;D;T;.

Eigen

Pathogenic

0.90

Eigen_PC

Pathogenic

0.86

FATHMM_MKL

Uncertain

0.97

M_CAP

Benign

0.023

MetaRNN

Benign

0.33

T;T;T;T;T;T

MetaSVM

Benign

-0.72

MutationAssessor

Uncertain

2.3

.;.;M;M;.;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-2.7

.;D;D;D;.;D

REVEL

Benign

0.27

Sift

Uncertain

0.0010

.;D;D;D;.;D

Sift4G

Uncertain

0.012

D;D;D;D;D;D

Polyphen

1.0, 1.0

.;D;D;D;D;.

Vest4

0.40

MutPred

0.28

.;.;Loss of MoRF binding (P = 0.0333);Loss of MoRF binding (P = 0.0333);.;.;

MVP

0.58

MPC

0.74

ClinPred

0.98

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.56

gMVP

0.69

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over